Cerebral protection during surgical procedures requiring circulatory arrest of low flow remains the factor that most limits the critical time for repair of lesions. In-vivo (31)p-nuclear magnetic resonance spectroscopy (NMR) was used to assess the metabolic state of the brain during circulatory arrest by measuring the concentration of high energy phosphate compounds (HEP) and the intracellular pH (pHi). The degree of cerebral protection during deep hypothermic cardiopulmonary bypass (CPB) at low flow rates was compared to that obtained with a period of circulatory arrest interrupted by intermittent systemic perfusion. Sheep were instrumented with cannulae for CPB and a radiofrequency coil was positioned onto the skull. Animals were placed in the bore of a 4.7T magnet, cooled on CPB to 15 degrees C., and had either circulatory arrest (n=5) or continuous low flow rates of 5ml/kg/min (n=6) or 10ml/kg/min (n=7) for 2 hours. A fourth group (n=5) underwent one hour of circulatory arrest, systemic perfusion for 30 minutes, then another hour of circulatory arrest. Both circulatory arrest and a flow of 5ml/kg/min resulted in severe intracellular acidosis and depletion of HEP. A flow of 10ml/kg/min preserved HEP and pHi. Therefore, deep hypothermia with CPB flows as low as 10ml/kg/min can maintain brain high energy phosphate concentrations and intracellular pH for 2 hours in sheep, whereas flows of 5 ml/kg/min or intermittent full-flow systemic perfusion between periods of circulatory arrest offer minimal benefit. Previous studies from our laboratory have shown that these NMR findings positively correlate with improved survival and preservation of neurological function.